Pulmonary hypertension in juvenile-onset systemic lupus erythematosus: a case series.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a rare multisystem autoimmune disorder with a variable clinical phenotype. Pulmonary hypertension (PHTN) is a recognised (and not uncommonly asymptomatic) complication of the condition with an associated poor prognosis in adults. It is relatively rare in juvenile-onset SLE (JSLE). METHODS: We present a retrospective descriptive case series of four female children aged 4 to 15 years at presentation of JSLE and aged 8 to 27 years at time of diagnosis of PHTN from the United Kingdom. All cases were identified through the UK JSLE Cohort Study. RESULTS: Of 665 children with JSLE in the UK cohort study to date (data from 2006-2020), four (0.6%) were identified as having PHTN. 3/4 of the PHTN cases presented with cardiovascular symptoms and / or signs at presentation.3/4 were treated with Rituximab and had a good long-term outcome. Shared clinical features include high baseline disease activity scores. CONCLUSIONS: JSLE has a high associated cardiovascular morbidity and mortality and early identification of treatable complications such as PHTN is vital. We suggest that children with high baseline disease activity scores and those presenting with cardiovascular symptoms and signs are most likely to have concurrent PHTN. Routine echocardiography is an effective screening tool and should be used as part of a standard diagnostic work-up.

Contiguous gene deletion in a Chinese family with X-linked nephrogenic diabetes insipidus: challenges in early diagnosis and implications for affected families.

Nephrogenic diabetes insipidus (NDI) is a rare disorder of the renal collecting tubules, characterized by an inability to concentrate urine due to an impaired response to arginine vasopressin (AVP), resulting in dilute urine and polyuria. Causes of NDI are heterogeneous and diagnosing congenital NDI (cNDI) in young infants is clinically challenging, as typical symptoms are often unappreciated or inconspicuous. Instead, young infants may present with non-specific signs such as vomiting, poor feeding, failure to thrive, unexplained fevers, irritability, constipation or diarrhea. We report a 37-day-old infant who presented with polyuria and severe hypernatremic dehydration that was unresponsive to vasopressin. The patient was treated with amiloride, indomethacin and hydrochlorothiazide. Genetic analysis revealed a novel contiguous deletion involving the entire AVPR2 gene and the last exon of the adjacent ARHGAP4 gene. A study of the family confirmed the carrier status in the mother. This case illustrates the importance of molecular testing in confirming the diagnosis in the index patient, as well as in identifying asymptomatic at-risk female carriers so that appropriate genetic counselling can be given for reproductive planning. All pediatric patients with suspected cNDI should undergo genetic analysis for a definitive diagnosis.

Risk factors for damage in childhood-onset systemic lupus erythematosus in Asians: a case control study.

BACKGROUND: Accumulated damage is an important prognostic factor in systemic lupus erythematous. However, the pattern of disease damage and its risk factors have not been well studied in childhood-onset systemic lupus erythematosus (cSLE) in Asia. The objectives are to evaluate the pattern of damage and to identify the risk factors for accumulated damage in an Asian group of cSLE. METHODS: A retrospective chart review was conducted on a group of 59 patients with cSLE. Patient demographics and clinical variables were first collected at diagnosis. Over the course of their disease, clinical variables considered as risk factors for damage were also collected. Damage was measured using the Systemic Lupus International Collaborating Clinics/ American College of Rheumatology Damage Index (SDI) for each patient at their last encounter. Based on their SDI scores, patients were then dichotomized to two groups: a group with presence of disease damage (SDI ≥1) and a group with absence of disease damage (SDI score = 0). Clinical variables including age at diagnosis, gender, ethnicity, disease duration, disease manifestations, laboratory values at diagnosis, disease activity at diagnosis and last encounter, major organ involvement, number of lupus flares, major infection, and intensity of immunosuppressive medications were compared between the two groups. Growth failure and estimated glomerular filtration rate (eGFR) were also analysed as secondary outcomes. RESULTS: After a median disease duration and follow up of 7.8 years, 39 patients (66.1%) had no disease damage while 20 patients (33.9%) had acquired disease damage. Disease damage most frequently occurred in the ocular (15.3%), neuropsychiatric (11.9%) and musculoskeletal (11.9%) domains. The most frequent forms of damage were cataracts (11.9%), and avascular necrosis (unilateral and bilateral combined 10.2%). After controlling for other variables, presence of neuropsychiatric manifestations remained the only statistically significant risk factor for damage. The rate of growth failure in our group of patients was 16%. Patients who experienced growth failure were significantly younger at disease diagnosis. The median age of diagnosis was 10 for those who experienced growth failure, whereas the median age of diagnosis was 13 for those who did not experience growth failure. Despite a high rate of renal involvement in the group (79.7%), renal damage was only seen in 3.2% of the patients. 91.5% of the studied group had normal eGFR of ≥90 ml/min/1.73m2 at their last follow up. CONCLUSION: This group of patients had a low rate of damage accrual, with one of the lowest rates in renal damage when compared to other cohorts reported. The presence of neuropsychiatric manifestations was identified as the most significant risk factor for disease damage, while the most frequent forms of damage were cataracts and avascular necrosis, which were both related to prolonged steroid use. Despite the limitations of this study, it highlights the need for larger prospective studies to understand the relationship between childhood-onset SLE and its resulting damage.